1. Academic Validation
  2. CACNA1H restrains chemotherapy resistance in ovarian clear cell carcinoma cells by repressing autophagy

CACNA1H restrains chemotherapy resistance in ovarian clear cell carcinoma cells by repressing autophagy

  • Mol Genet Genomics. 2024 Aug 6;299(1):77. doi: 10.1007/s00438-024-02165-y.
Huaijing Shi 1 Liang Zheng 2 Xinyan Jiang 1 Hongju Chen 3
Affiliations

Affiliations

  • 1 Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Folma Road, Jin'an District, Fuzhou, 350014, Fujian, China.
  • 2 Department of Abdominal Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, 350014, China.
  • 3 Department of Gynecology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, No. 420 Folma Road, Jin'an District, Fuzhou, 350014, Fujian, China. ChenhongJuu@163.com.
Abstract

Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian Cancer and is highly malignant with high chemoresistance. CACNA1H is pivotal in tumor development. However, the role of CACNA1H in the acquisition process of chemotherapeutic resistance in OCCC cells is rarely reported. Therefore, this study aimed to explore the role of CACNA1H in chemotherapy resistance of OCCC cells and its related mechanism. Based on bioinformatics analysis, we found that CACNA1H was downregulated in chemoresistant OCCC patients compared to chemosensitive OCCC patients. Comparing DDP-resistant and sensitive OCCC cell lines, the resistant strain showed lower CACNA1H mRNA expression. CACNA1H expression was associated with calcium signaling pathways in chemoresistant OCCC patients. CACNA1H mRNA expression was significantly downregulated in OCCC cells compared to normal ovarian epithelial cells. When CACNA1H was overexpressed, intracellular CA2+ concentration and protein levels of p-CaMKII and p-Akt were significantly upregulated, while protein levels of LC3-II/LC3-I and Beclin1 were downregulated, indicating a repression of Autophagy. The rescue experiment revealed that CACNA1H overexpression in drug-resistant OCCC cells reduced autophagy-induced DDP resistance via CaMKII/Akt signaling. Overall, CACNA1H increased intracellular CA2+ concentration and activated CaMKII/Akt signaling pathway in OCCC, thereby repressing Autophagy to maintain the sensitivity of OCCC cells to DDP.

Keywords

Autophagy; CACNA1H; Chemoresistance; Ovarian clear cell carcinoma.

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